Process for producing cyclohexenone long-chain alcohols

ABSTRACT

A process for producing cyclohexenone long-chain alcohol represented by the following formula (1): (wherein A represents a C10-C18 alkylene or alkenylene group, and each of R 1 , R 2 , and R 3  individually represents hydrogen or methyl), comprising reacting a 3-alkoxy-2-cyclohexen-1-one derivative represented by the following formula (2): (wherein R 1 , R 2 , and R 3  have the same meanings as above, and R 4  represents a C1-C5 alkyl group) with a Grignard&#39;s reagent prepared by protecting the hydroxyl groups of C10-C18 ω-halogenoalcohol through silylation, and hydrolyzing the resultant reaction product. The process of the present invention for producing cyclohexenone long-chain alcohol requires a reduced number of reaction steps, can be performed with ease and with reduced production cost, and thus finds utility in the industry

TECHNICAL FIELD

The present invention relates to a process for producing a cyclohexenonelong-chain alcohol, which process requires a reduced number of reactionsteps and can be performed with ease and is thus industriallyadvantageous.

BACKGROUND ART

Nerve growth factor (NGF), which is found in particular abundance in thehippocampus and cerebral cortex of the brain, is a neurotrophic factorwhich is required by a living body for sustaining life and functions andstimulates differentiation and growth of neurons. In the brain, NGF actson cholinergic neurons. Alzheimer's disease is accepted to exhibit aprimary lesion of regeneration and falling of cholinergic neurons, andon the basis of this understanding, NGF has been administered to thebrain as therapy for the disease.

However, NGF, being a protein having a molecular weight of 12,000,cannot pass through the blood-brain barrier, and thus does not serve aspractical means for the treatment of Alzheimer's disease.

Meanwhile, cyclohexenone long-chain alcohol has a low molecular weightand is known to be useful as a prophylactic or therapeutic drug forcerebral diseases such as dementia, in view that, when administeredorally, the alcohol reaches the brain, passes through the blood-brainbarrier, and at low concentration exhibits excellent effect to stimulategrowth of neurons, to thereby directly act on neurites to elicitextension (Japanese Kohyo (PCT) Patent Publication No. 2001-515058).

Hitherto, cyclohexenone long-chain alcohol has been produced through acomplicated process; for example, by reacting cyclohexanone ormethyl-substituted 2-cyclohexen-1-one with benzenesulfinate in thepresence of acid, then with ethylene glycol to form a ketal compound,and further with ω-halogenoalcanol, followed by treatment with an acidto remove a protective group. Specifically, in the case of production of3-(14-hydroxytetradecyl)-4-methyl-2-cyclohexen-1-one from a startingmaterial 3-methylcyclohexenone, seven reaction steps have conventionallybeen required.

DISCLOSURE OF THE INVENTION

As described above, the conventional process for producing cyclohexenonelong-chain alcohol requires a number of complicated and intricate steps,involves high production cost, and is thus industrially disadvantageous.

Accordingly, an object of the present invention is to provide anindustrially advantageous process for producing cyclohexenone long-chainalcohol, which process requires a reduced number of reaction steps andcan be performed with ease and at reduced production cost.

The present inventors have performed extensive studies for developing asimple, convenient process for producing cyclohexenone long-chainalcohol starting from a known substance, and have found that whencyclohexenone of enol form—which can be produced with ease from a knownsubstance 1,3-cyclohexanedione—is subjected to Grignard reaction by useof ω-halogeno long-chain alcohol whose hydroxyl group is protectedthrough silylation, cyclohexenone long-chain alcohol can be obtainedthrough a reduced number of steps, conveniently, at low production cost,and in an industrially advantageous manner, thus leading to completionof the invention.

Accordingly, the present invention provides a process for producingcyclohexenone long-chain alcohol represented by the following formula(1):

(wherein A represents a C10-C18 alkylene or alkenylene group, and eachof R¹, R², and R³ individually represents a hydrogen atom or a methylgroup), comprising reacting a 3-alkoxy-2-cyclohexen-1-one derivativerepresented by the following formula (2):

(wherein R¹, R², and R³ have the same meanings as above, and R⁴represents a C1-C5 alkyl group) with a Grignard's reagent prepared fromC10-C18 ω-halogenoalcohol whose hydroxyl group is protected throughsilylation, and hydrolyzing the resultant reaction product.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the starting compound represented by formula (2) (hereinafterreferred to as compound (2)), each of R¹, R², and R³ represents ahydrogen atom. Preferably, at least one of these is methyl. Thefollowing cases are particularly preferred: R¹=CH₃ and R²=R³=H, orR¹=R²=R³=CH₃. R⁴ represents a C1-C5 alkyl, with ethyl being particularlypreferred.

Examples of preferred starting compound (2) include3-ethoxy-6-methyl-2-cyclohexen-1-one,3-ethoxy-2,6-dimethyl-2-cyclohexen-1-one, and3-methoxy-2,6,6-trimethyl-2-cyclohexen-1-one.

The starting compound (2) can be obtained through enolation andmethylation of 1,3-cyclohexanedione, which is available at low cost. Thesequence in which enolation and methylation are carried out is notcritical, and enolation may precede methylation or vice versa. When allof R¹, R², and R³ are hydrogen atoms, methylation is not necessary.

Enolation may be performed by reacting 1,3-cyclohexanedione, which mayoptionally be methylated if necessary (e.g.,2-methyl-1,3-cyclohexanedione), with alcohol (R⁴OH) in the presence ofan acid catalyst. Examples of the acid catalyst includep-toluenesulfonic acid and sulfuric acid. The reaction is carried out ina solvent such as toluene, xylene, methanol, or ethanol, at 60-150° C.for 2 to 10 hours.

Methylation is performed by, for example, reacting enolated1,3-cyclohexanedione, which may optionally be enolated if necessary,with a lithiation reagent such as lithium diisopropylamide obtainedthrough reaction between alkyl lithium and diisopropylamine, then with amethylation agent such as methyl iodide. The lithiation reaction ispreferably performed by cooling a solution prepared by adding lithiumdiisopropylamine to tetrahydrofuran or hexane to −80 to 0° C. (e.g.,−78° C.), then adding optionally enolated 1,3-cyclohexanedione(preferably 3-ethoxy-2-cyclohexan-1-one) dissolved in tetrahydrofuran,hexane, etc. Preferably, methylation is performed after adding methyliodide to the resultant reaction mixture and heating the mixture to 5 to30° C. (e.g., room temperature), while stirring the mixture for 5 to 12hours.

The thus-obtained compound (2) is reacted with a Grignard's reagentprepared from C10-C18 ω-halogenoalcanol whose hydroxy group is protectedthrough silylation, and is then subjected to hydrolysis, to therebyproduce a cyclohexenone long-chain alcohol (1). Examples of the C10-C18ω-halogenoalcanol which has undergone silylation include the compoundrepresented by the following formula (3):

(wherein X represents a halogen atom, A represents a C10-C18 alkylene oralkenylene group, and each of R⁵, R⁶, and R⁷ represents a C1-C8 alkylgroup). Examples of X include Cl, Br, and I, with Br being preferred.Examples of A include C10-C18 linear or branched alkylene or alkenylenegroups, with C12-C16 linear or branched alkylene groups being morepreferred, and C12-C16 linear alkylene groups being even more preferred,and tetradecylene and pentadecylene being most preferred. Examples ofR⁵, R⁶, and R⁷ include a methyl group, an ethyl group, an isopropylgroup, and a t-butyl group.

The Grignard's reagent used in the present invention can be obtained bya conventional method, through reaction between a silylatedω-halogenoalcanol and magnesium.

The reaction between the compound (2) and the Grignard's reagent isperformed in the manner of an ordinary Grignard reaction, and preferablyin an absolute solvent such as diethyl ether or tetrahydrofuran at40-80° C. for 0.5 to 3 hours.

The subsequent hydrolysis is preferably performed in the presence of anacid such as p-toluenesulfonic acid, hydrochloric acid, or sulfuricacid. Through hydrolysis, the group R⁴, the Grignard's reagent, and thesilylation-protective group are removed.

In each reaction step of the process of the present invention, theresultant intermediate may be isolated and then forwarded to the nextreaction step. However, the intermediate may be forwarded directly tothe next reaction step, without being isolated. In the presentinvention, the intermediate or a target compound can be isolated from areaction mixture through washing, extraction, recrystallization,chromatographic techniques, etc., solely or in combination.

EXAMPLES

The present invention will next be described by way of Examples, whichshould not be construed as limiting the invention thereto.

Example 1 Synthesis of3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one (1)Synthesis of 3-ethoxy-2-methyl-2-cyclohexen-1-one

2-Methyl-1,3-cyclohexanedione (3 g, 23.8 mmol) was dissolved in amixture of ethanol (30 mL) and toluene (56 mL), and to the resultantmixture, p-toluenesulfonic acid (92 mg, 0.47 mmol) was added. Themixture was allowed to react while refluxing with heat. Subsequently,the water/ethanol/toluene azeotrope (boiling point: 78° C.) wasdistilled off, and the remaining toluene was removed under reducedpressure. The crude product was purified by silica gel flashchromatography (ethyl ether/hexane=8/2), to thereby yield 2.7 g (17.4mmol) of 3-ethoxy-2-methyl-2-cyclohexen-1-one.

Yield: 73%

R_(f) (ethyl ether/hexane=80/20)=0.37

¹H-NMR(200 MHz, CDCl₃) δ: 1.32(t, ³J=7.00 Hz, 3H, H-9), 1.67(t, ⁴J=1.49Hz, 3H, H-7), 1.94(qn, ³J=6.33 Hz, 2H, H-5), 2.31(t, ³J=6.62 Hz, 2H,H-6), 2.51(td, ³J=6.12 Hz, ⁴J=1.44 Hz, 2H, H-4), 4.03(q, ³J=7.00 Hz, 2H,H-8).

¹³C-NMR(50 MHz, CDCl₃) δ: 7.4(C-7), 15.4(C-9), 21.1(C-5), 25.4(C-4),36.4(C-6), 63.5(C-8), 115.1(C-2), 171.4(C-3), 198.9(C-1).

(2) Synthesis of 3-ethoxy-2,6-dimethyl-2-cyclohexen-1-one:

Diisopropylamine (2.35 mL, 19.45 mmol) dissolved in tetrahydrofuran (8mL) was cooled to −78° C., n-butyllithium (12.96 mL, 19.45 mmol) wasadded thereto, and the temperature was elevated to 0° C. After havingbeen stirred for 2 hours at 0° C., the reaction mixture was cooled to−78° C., and 3-ethoxy-2-methyl-2-cyclohexen-1-one (2 g, 12.96 mmol)dissolved in tetrahydrofuran (5 mL) was added thereto. One hour later,methyl iodide (1.21 mL, 19.45 mmol) was added thereto, and thetemperature of the reaction mixture was allowed to rise to roomtemperature. The reaction mixture was stirred overnight, diluted withwater (100 mL), and then extracted three times with ethyl ether. Theorganic layers were combined, washed with an aqueous NaCl solution,dried over magnesium sulfate, filtered, and concentrated under reducedpressure. The crude product was applied to silica, and purified by meansof silica gel column chromatography (ethyl ether/hexane=4/6), to therebyyield 1.72 g (10.24 mmol) of 3-ethoxy-2,6-dimethyl-2-cyclohexen-1-one.

Yield: 79%

R_(f) (ethyl ether/hexane=40/60)=0.9

¹H-NMR(200 MHz, CDCl₃) δ: 1.12(d, 3H, H-8), 1.33(t, ³=7.00 Hz, 3H,H-10), 1.5 4-1.74(m, 4H, H-5, H-7), 1.98-2.11(m, 1H, H-5′), 2.19-2.31(m,1H, H-6), 2.51-2.6 0(m, 2H, H-4), 4.04(qd, J=4.68 Hz, J=2.33 Hz, 2H,H-9).

¹³C-NMR(50 MHz, CDCl₃) δ: 7.4(C-7), 15.3 and 15.7(C-8, C-10), 24.5(C-5),28.9(C-4), 39.5(C-6), 63.3(C-9), 114.3(C-2), 170.2(C-3), 201.2(C-1).

(3) Synthesis of 3-ethoxy-2,6,6-trimethyl-2-cyclohexen-1-one

Diisopropylamine (1.45 mL, 10.34 mmol) dissolved in tetrahydrofuran (3mL) was cooled to −78° C., n-butyllithium (8.7 mL, 10.46 mmol) was addedthereto, and the temperature was elevated to 0° C. After having beenstirred for 2 hours at 0° C., the reaction mixture was cooled to −78°C., and 3-ethoxy-2,6-dimethyl-2-cyclohexen-1-one (1.47 g, 8.72 mmol)dissolved in tetrahydrofuran (6 mL) was added thereto. One hour later,methyl iodide (1.59 mL, 10.46 mmol) was added thereto, and thetemperature of the reaction mixture was allowed to rise to roomtemperature. The reaction mixture was stirred overnight, diluted withwater (100 mL), and then extracted three times with ethyl ether. Theorganic layers were combined, washed with an aqueous NaCl solution,dried over magnesium sulfate, filtered, and concentrated under reducedpressure. The crude product was purified by silica gel columnchromatography (ethyl ether/hexane=4/6), to thereby yield 1.46 g (8.04mmol) of 3-ethoxy-2,6,6-trimethyl-2-cyclohexen-1-one.

Yield: 92.2%

R_(f) (ethyl ether/hexane=40/60)=0.31

¹H-NMR(200 MHz, CDCl₃) δ: 1.03(s, 6H, H-8, H-9), 1.30(t, ³J=7.01 Hz,3H-11), 1.64 (t, ⁴J=1.6 Hz, 3H, H-7), 1.75(t, ³J=6.27 Hz, 2H, H-5),2.51(tq, ³J=6.29 Hz, ⁴J=1.5 6 Hz, 2H, H-4), 4.01(q, ³J=6.97 Hz, 2H,H-10).

¹³C-NMR(50 MHz, CDCl₃) δ: 8.0(C-7), 15.4(C-11), 22.6(C-4), 24.7(C-8,C-9), 34.7(C-5), 39.5(C-6), 63.2(C-10), 113.1(C-2), 169.0(C-3),203.6(C-1).

(4) Synthesis of 15-bromo-1-(t-butyldimethylsiloxy)-pentadecane

(a) Synthesis of 1,15-pentadecanediol

Pentadecanolide (5 g, 20.8 mmol) dissolved in tetrahydrofuran (150 mL)was cooled to 0° C., and to the resultant solution, aluminum lithiumhydride (1.2 g, 31.2 mmol) was added in portions. The temperature of themixture was then returned to room temperature. The reaction mixture wasstirred for three days at room temperature, and subsequently, an aqueoussaturated tartaric acid solution (200 mL) was added thereto at 0° C. Themixture was subjected to extraction with ethyl ether three times. Theorganic layers were combined, washed with aqueous sodium chloridesolution, dried over magnesium sulfate, filtered, and concentrated underreduced pressure, to thereby yield 5.01 g (20.5 mmol) of1,15-pentadecanediol.

Yield: 98.6%

R_(f) (hexane/ethyl acetate=10/90)=0.44

Melting point: 84-85° C.

¹H-NMR(200 MHz, CDCl₃) δ: 1.28(s large, 22H, H-3 to H-13), 1.56(qn,³J=6.6 Hz, 4H, H-2, 14), 3.64(t, ³J=6.6 Hz, 4H, H-1, 15).

¹³C-NMR(50 MHz, CDCl₃) δ: 26.5(C-3, 13), 29.9(C-4 to C-12), 33.7(C-2,C-14), 62.1(C-1, 15).

(b) Synthesis of 15-bromo-pentadecan-1-ol

48% Hydrogen bromide (50 mL) was gradually added to a mixture of1,15-pentadecanediol (5.08 g, 20.8 mmol) and cyclohexane (50 mL), andthe resultant mixture was refluxed with heat for 6 hours, followed byseparation into two layers. The aqueous layer was subjected toextraction with hexane three times. The organic layers were combined,washed with aqueous saturated sodium hydrogencarbonate solution andaqueous sodium chloride solution, dried over magnesium sulfate, andconcentrated under reduced pressure. The crude product was applied tosilica for purification by means of silica gel column chromatography(hexane/ethyl acetate=7/3), to thereby yield 4.33 g (14.08 mmol) of15-bromo-pentadecan-1-ol.

Yield: 68%

R_(f) (hexane/ethyl acetate=60/40)=0.47

Melting point: 61-63° C.

¹H-NMR(200 MHz, CDCl₃) δ: 1.28(s large, 22H, H-3 to H-13), 1.57(qn,³J=6.7 Hz, 2H, H-2), 1.86(qn, ³J=6.8 Hz, 2H, H-14), 3.41(t,³J=6.8 Hz,2H, H-15), 3.65(t, ³J=6.6 Hz, 2H, H-1).

¹³C-NMR(50 MHz, CDCl₃) δ: 25.5(C-3), 28.1(C-13), 28.5(C-12), 29.4(C-4 toC-11), 32.7(C-2,C-15), 33.8(C-14), 62.9(C-1).

(c) Synthesis of 15-bromo-1-(t-butyldimethylsiloxy)-pentadecane

15-Bromo-pentadecan-1-ol (2.3 g, 7.49 mmol) dissolved in methylenechloride (23 mL) was mixed with trimethylamine (2.1 mL, 14.98 mmol),t-butyldimethylsilyl chloride (2.03 g, 13.48 mmol), anddimethylaminopyridine (457.6 mg, 3.74 mmol). The mixture was stirred forone hour at room temperature. Subsequently, aqueous saturated ammoniumchloride solution was added to the reaction mixture for separation intoa methylene chloride layer (200 mL) and an aqueous layer (200 mL). Theorganic layer was dried over magnesium sulfate, filtered, andconcentrated under reduced pressure. The crude product was purified bymeans of silica gel column flash chromatography (hexane/ethylacetate=99/1), to thereby afford 2.98 g (7.07 mmol) of15-bromo-1-(t-butyldimethylsiloxy)pentadecane.

Yield: 94.4%

R_(f) (hexane=100)=0.43

¹H-NMR(200 MHz, CDCl₃) δ: 0.00(s, 6H, Me), 0.85(s, 9H, tBu), 1.21(slarge, 22H, H-3 to H-13), 1.33-1.46(m, 2H, H-2), 1.74-1.88(m, 2H, H-14),3.36(t, ³J=6.89 Hz, 2H, H-15), 3.55(t, ³J=6.52 Hz, 2H, H-1).

¹³C-NMR(50 MHz, CDCl₃) δ: −5.2(Me), 26(tBu), 28.2-29.7(C-3 to C-13),33(C-15), 35(C-2, C-14), 63(C-1).

(5) Synthesis of3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one

15-Bromo-1-(t-butyldimethylsiloxy)pentadecane (1 g, 2.36 mmol) dissolvedin absolute ethyl ether (3 mL) and magnesium (0.115 g) were mixed, andthe mixture was refluxed for 40 minutes. Subsequently,3-ethoxy-2,6,6-trimethyl-2-cyclohexen-1-one (287.5 mg, 1.57 mmol)dissolved in tetrahydrofuran (2 mL) was added thereto. After stirringthe mixture for four hours, 10% hydrochloric acid (3 mL) was added, andthe reaction was allowed to continue for a further 17 hours understirring. The reaction mixture was neutralized with sodiumhydrogencarbonate, followed by extraction with ethyl ether three times.The organic layers were combined, washed with aqueous sodium chloridesolution, dried over magnesium sulfate, filtered, and concentrated underreduced pressure. The crude product was purified by means of silica gelcolumn chromatography (hexane/ethyl acetate=9/1-6/4; concentrationgradient=5%), to thereby afford 222.7 mg (0.61 mmol) of3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one.

Yield: 39%

R_(f) (hexane/ethyl acetate=70/30)=0.26

Melting point: 29-30° C.

¹H-NMR(200 MHz, CDCl₃) δ: 1.06(s, 6H, H-22, 23), 1.17(m, 24H, H-8 aH-19), 1.47 (m, 2H, H-20), 1.68(s, 3H, H-24), 1.72(t, J=7.14 Hz, 2H,H-5), 2.07(m, 2H, H-7), 2.33(t, J=6.9 Hz, 2 H, H-6), 3.55(t, J=6.64 Hz,2H, H-21).

¹³C-NMR(50 MHz, CDCl₃) δ: 11.4(C-24), 25.8(C-19), 26.8(C-22, 23),28.8(C-8), 29.2-29.6(C-10 a C-18), 30.5(C-7), 30.9(C-9), 32.7(C-20),34.2(C-5), 36.2(C-4), 37.4(C-6), 62.8(C-21), 130.5(C-2), 165.6(C-3),199.1(C-1).

Example 2 Synthesis of3-(14-hydroxytetradecyl)-4-methyl-2-cyclohexen-1-one (1) Synthesis of3-ethoxy-6-methyl-2-cyclohexen-1-one

Diisopropylamine (3.4 mL, 24.4 mmol) dissolved in tetrahydrofuran (50mL) was cooled to −78° C., n-butyllithium (8.2 mL, 12.3 mmol) was addedthereto, and the temperature was elevated to 0° C. After having beenstirred for 2 hours at 0° C., the reaction mixture was cooled to −78°C., and 3-ethoxy-2-cyclohexen-1-one (1.54 g, 11 mmol) dissolved intetrahydrofuran (3 mL) was added thereto. After 2 hours of reaction,methyl iodide (0.77 mL, 12.4 mmol) was added, and the temperature of thereaction mixture was allowed to rise to room temperature. The reactionmixture was stirred for 18 hours at room temperature. Water (100 mL) wasadded thereto, and the resultant mixture was subjected to extractionthree times with ethyl ether. The organic layers were combined, washedwith an aqueous NaCl solution, dried over magnesium sulfate, filtered,and concentrated under reduced pressure. The crude product was purifiedby flash chromatography (ethyl ether/hexane=40/60), to thereby yield1.19 g (7.7 mmol) of 3-ethoxy-6-methyl-2-cyclohexen-1-one.

Yield: 73%

R_(f) (hexane/ethyl acetate=70/30)=0.41

¹H-NMR(200 MHz, CDCl₃) δ: 1.13(d, ³J=6.87 Hz, 3H, H-7), 1.33(t, ³J=7.01Hz, 3H, 0CH₂CH ₃), 1.68(m, 1H, H-5), 2.03(m, 1H, H-5′), 2.26(m, 1H,H-6), 2.39(m, 2H, H-4), 3.85(q, ³J=7.04 Hz, 2H, 0CH ₂CH₃), 5.28(s, 1H,H-2).

¹³C-NMR(50 MHz, CDCl₃) δ: 15.03(C-7), 16.28(0CH₂ CH₃), 29.33(C-4),30.18(C-5), 41.03(C-6), 65.06(0CH₂CH₃), 102.92(C-2), 177.75(C-3),202.86(C-1).

(2) Synthesis of 3-(14-hydroxytetradecyl)-4-methyl-2-cyclohexen-1-one

14-Bromo-1-(t-butyldimethylsiloxy)tetradecane (1.814 g, 4.45 mmol)dissolved in absolute ethyl ether (4 mL) and magnesium (0.216 g, 8.9mmol) were mixed, and dibromoethane was added dropwise to the resultantmixture, to thereby initiate Grignard reaction. The reaction was allowedto continue for 30 minutes. 3-Ethoxy-6-methyl-2-cyclohexen-1-one (0.825g, 5.32 mmol) dissolved in tetrahydrofuran (4 mL) was added thereto. Themixture was stirred for 24 hours at room temperature. Subsequently, 10%hydrochloric acid (10 mL) was added for reaction under stirring for afurther 24 hours. The reaction mixture was neutralized with saturatedsodium hydrogencarbonate solution (10 mL) then subjected to extractionwith ethyl ether (15 mL) three times. The organic layers were combined,washed with an aqueous NaCl solution, dried over magnesium sulfate,filtered, and concentrated under reduced pressure. The crude product waspurified by means of flash chromatography (ethyl ether/hexane=70/30), tothereby yield 0.768 g (2.74 mmol) of3-(14-hydroxytetradecyl)-4-methyl-2-cyclohexen-1-one.

Yield: 55%

R_(f) (ethyl ether/hexane=70/30)=0.30

Melting point: 37-38° C.

¹H-NMR(200 MHz, CDCl₃) δ: 1.18(d, ³J=7.13 Hz, 3H, H-21), 1.25-1.59(m,24H, H-8 to H-19), 1.69-1.84(m, 1H, H-5), 2.01-2.57(m, 6H,H-5′/H-7/H-6/H-7′/H-4/H-6′), 3.63(t, ³J=6.50 Hz, 2H, H-20), 5.80(s, 1H,H-2).

¹³C-NMR(50 MHz, CDCl₃) δ: 17.82(C-21), 25.76(C-5), 27.20-32.82(C-8 toC-19), 33.07(C-4), 34.23(C-7), 35.67(C-6), 63.07(C-20), 124.92(C-2),170.72(C-3), 199.82(C-1).

INDUSTRIAL APPLICABILITY

The process of the present invention for producing cyclohexenonelong-chain alcohol involves a reduced number of reaction steps, can beperformed with ease at reduced production cost, and thus finds utilityin the industry.

1. A process for producing cyclohexenone long-chain alcohol representedby the following formula (1):

(wherein A represents a C10-C18 alkylene or alkenylene group, and eachof R¹, R², and R³ individually represents a hydrogen atom or a methylgroup), comprising reacting a 3-alkoxy-2-cyclohexen-1-one derivativerepresented by the following formula (2):

(wherein R¹, R², and R³ have the same meanings as above, and R⁴represents a C1-C5 alkyl group) with a Grignard's reagent prepared fromC10-C18 ω-halogenoalcohol whose hydroxyl group is protected throughsilylation, and hydrolyzing the resultant reaction product.